Yu-Fa Su1, Eing-Mei Tsai2, Chih-Chieh Chen3, Chun-Chieh Wu4, Tze-Kiong Er5. 1. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 2. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Headquarters of the Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan. 3. Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan. 4. Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 5. Division of Laboratory Medicine, Asia University Hospital, Asia University, Taichung, Taiwan; Department of Food Nutrition and Health Biotechnology, Asia University, Taichung, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan. Electronic address: tzekiong92@gmail.com.
Abstract
BACKGROUND: The objective of this study was to assess the mutational profile in epithelial ovarian cancer using formalin-fixed, paraffin-embedded (FFPE) tumor specimens from a Taiwanese population by performing targeted sequencing of 9 cancer-associated genes. METHODS: Targeted sequencing was performed on 32 formalin-fixed, paraffin embedded (FFPE) tumor specimens, consisting of matched samples from 16 epithelial ovarian cancer patients. Genetic alterations in the 9 cancer-associated genes were detected using a deep sequencing (>1000×) approach. RESULTS: ARID1A and PIK3CA were the most frequently mutated genes. Specifically, ARID1A mutations and PIK3CA mutations were detected in 77.8% and 66.7% of ovarian clear cell carcinoma patients, respectively. Mutations in other genes, including MLH1 (6.3%) and CREBBP (6.3%), were detected in the Taiwanese population. We also identified coexisting ARID1A-PIK3CA mutations (43.8%) and ARID1A-KRAS mutations (12.5%) in tumors. It should also be noted that we identified the presence of three coexisting mutations, the ARID1A-KRAS-PIK3CA mutations and the ARID1A-CREBBP-PIK3CA mutations. CONCLUSIONS: In summary, we identified novel genetic alterations in patients with epithelial ovarian carcinoma (EOC) in a Taiwanese populations. Further studies are needed to elucidate the mechanism of chromatin remodeling to examine the role of the PI3K/AKT pathway, to determine the critical roles of these mechanisms in tumor development and the progression of ovarian malignancy and to investigate new targeted therapies. Overall, our findings were reliable and are worthy of further study.
BACKGROUND: The objective of this study was to assess the mutational profile in epithelial ovarian cancer using formalin-fixed, paraffin-embedded (FFPE) tumor specimens from a Taiwanese population by performing targeted sequencing of 9 cancer-associated genes. METHODS: Targeted sequencing was performed on 32 formalin-fixed, paraffin embedded (FFPE) tumor specimens, consisting of matched samples from 16 epithelial ovarian cancerpatients. Genetic alterations in the 9 cancer-associated genes were detected using a deep sequencing (>1000×) approach. RESULTS:ARID1A and PIK3CA were the most frequently mutated genes. Specifically, ARID1A mutations and PIK3CA mutations were detected in 77.8% and 66.7% of ovarian clear cell carcinomapatients, respectively. Mutations in other genes, including MLH1 (6.3%) and CREBBP (6.3%), were detected in the Taiwanese population. We also identified coexisting ARID1A-PIK3CA mutations (43.8%) and ARID1A-KRAS mutations (12.5%) in tumors. It should also be noted that we identified the presence of three coexisting mutations, the ARID1A-KRAS-PIK3CA mutations and the ARID1A-CREBBP-PIK3CA mutations. CONCLUSIONS: In summary, we identified novel genetic alterations in patients with epithelial ovarian carcinoma (EOC) in a Taiwanese populations. Further studies are needed to elucidate the mechanism of chromatin remodeling to examine the role of the PI3K/AKT pathway, to determine the critical roles of these mechanisms in tumor development and the progression of ovarian malignancy and to investigate new targeted therapies. Overall, our findings were reliable and are worthy of further study.
Authors: Senthil Damodaran; Fengmin Zhao; Dustin A Deming; Edith P Mitchell; John J Wright; Robert J Gray; Victoria Wang; Lisa M McShane; Larry V Rubinstein; David R Patton; P Mickey Williams; Stanley R Hamilton; Jennifer M Suga; Barbara A Conley; Carlos L Arteaga; Lyndsay N Harris; Peter J O'Dwyer; Alice P Chen; Keith T Flaherty Journal: J Clin Oncol Date: 2022-02-08 Impact factor: 50.717